Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders.

When O2 availability is reduced unavoidably, as it is at high altitude, a potential mechanism to improve O2 delivery to tissues is an increase in blood flow. Nitric oxide (NO) regulates blood vessel diameter and can influence blood flow. This field study of intrapopulation variation at high altitude tested the hypothesis that the level of exhaled NO (a summary measure of pulmonary synthesis, consumption, and transfer from cells in the airway) is directly proportional to pulmonary, and thus systemic, blood flow. Twenty Tibetan male and 37 female healthy, nonsmoking, native residents at 4,200 m (13,900 ft), with an average O2 saturation of hemoglobin of 85%, participated in the study. The geometric mean partial pressure of NO exhaled at a flow of 17 ml/s was 23.4 nmHg, significantly lower than that of a sea-level reference group. However, the rate of NO transfer out of the airway wall was seven times higher than at sea level, which implied the potential for vasodilation of the pulmonary blood vessels. Mean pulmonary blood flow (measured by cardiac index) was 2.7 +/- 0.1 (SE) l/min, and mean pulmonary artery systolic pressure was 31.4 +/- 0.9 (SE) mmHg. Higher exhaled NO was associated with higher pulmonary blood flow; yet there was no associated increase in pulmonary artery systolic pressure. The results suggest that NO in the lung may play a key beneficial role in allowing Tibetans at 4,200 m to compensate for ambient hypoxia with higher pulmonary blood flow and O2 delivery without the consequences of higher pulmonary arterial pressure.

[1]  S. Permutt,et al.  Modeling pulmonary nitric oxide exchange. , 2004, Journal of applied physiology.

[2]  M. Gassmann,et al.  Hypoxia and High Altitude , 2003 .

[3]  T. Giles,et al.  Adenoviral gene transfer of endothelial nitric-oxide synthase (eNOS) partially restores normal pulmonary arterial pressure in eNOS-deficient mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  C. Beall,et al.  Pulmonary nitric oxide in mountain dwellers , 2001, Nature.

[5]  D. Laskowski,et al.  High levels of exhaled nitric oxide (NO) and NO synthase III expression in lesional smooth muscle in lymphangioleiomyomatosis. , 2001, American journal of respiratory cell and molecular biology.

[6]  W. Hildebrandt,et al.  Hypoxia decreases exhaled nitric oxide in mountaineers susceptible to high-altitude pulmonary edema. , 2001, American journal of respiratory and critical care medicine.

[7]  K. Hirata,et al.  Reduced Hypoxic Pulmonary Vascular Remodeling by Nitric Oxide From the Endothelium , 2001, Hypertension.

[8]  D. Collen,et al.  Aerosol Gene Transfer With Inducible Nitric Oxide Synthase Reduces Hypoxic Pulmonary Hypertension and Pulmonary Vascular Remodeling in Rats , 2000, Circulation.

[9]  C. Sartori,et al.  Echocardiographic and invasive measurements of pulmonary artery pressure correlate closely at high altitude. , 2000, American journal of physiology. Heart and circulatory physiology.

[10]  D. Loukopoulos,et al.  Doppler-determined peak systolic tricuspid pressure gradient in persons with normal pulmonary function and tricuspid regurgitation. , 2000, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[11]  C. Sartori,et al.  Exhaled nitric oxide in high-altitude pulmonary edema: role in the regulation of pulmonary vascular tone and evidence for a role against inflammation. , 2000, American journal of respiratory and critical care medicine.

[12]  S. Permutt,et al.  Airway nitric oxide diffusion in asthma: Role in pulmonary function and bronchial responsiveness. , 2000, American journal of respiratory and critical care medicine.

[13]  P. Huang,et al.  The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia. , 1999, The Journal of clinical investigation.

[14]  Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide in Adults and Children — 1999 , 1999 .

[15]  N. Tsoukias,et al.  A two-compartment model of pulmonary nitric oxide exchange dynamics. , 1998, Journal of applied physiology.

[16]  Arthur S Slutsky,et al.  A significant proportion of exhaled nitric oxide arises in large airways in normal subjects. , 1998, Respiration physiology.

[17]  P. Huang,et al.  Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3. , 1998, The Journal of clinical investigation.

[18]  D. Laskowski,et al.  Nitric oxide synthesis in the lung. Regulation by oxygen through a kinetic mechanism. , 1998, The Journal of clinical investigation.

[19]  G. Hedenstierna,et al.  Nitric oxide from the human respiratory tract efficiently quantified by standardized single breath measurements. , 1997, Acta physiologica Scandinavica.

[20]  G. Koch,et al.  Effects of Long-term Infusion of Prostacyclin (Epoprostenol) on Echocardiographic Measures of Right Ventricular Structure and Function in Primary Pulmonary Hypertension , 1997 .

[21]  Arthur S Slutsky,et al.  Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. , 1997, American journal of respiratory and critical care medicine.

[22]  J. Stamler,et al.  Endothelium-derived nitric oxide regulates systemic and pulmonary vascular resistance during acute hypoxia in humans. , 1996, Journal of the American College of Cardiology.

[23]  A. Delabays,et al.  Inhaled nitric oxide for high-altitude pulmonary edema. , 1996, The New England journal of medicine.

[24]  P. Ganz,et al.  Role of nitric oxide in the local regulation of pulmonary vascular resistance in humans. , 1996, Circulation.

[25]  John L. Hankinson,et al.  Standardization of Spirometry, 1994 Update. American Thoracic Society. , 1995, American journal of respiratory and critical care medicine.

[26]  J. Stamler,et al.  Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. , 1994, Circulation.

[27]  S. Moncada,et al.  The L-arginine-nitric oxide pathway. , 1993, The New England journal of medicine.

[28]  G. Hedenstierna,et al.  Inhaled Nitric Oxide Selectively Reverses Human Hypoxic Pulmonary Vasoconstriction without Causing Systemic Vasodilation , 1993, Anesthesiology.

[29]  N. Schiller,et al.  Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. , 1990, The American journal of cardiology.

[30]  James Milledge,et al.  High altitude medicine and physiology , 1989 .

[31]  D. Lowe.  Aspects of Hypoxia , 1988 .

[32]  John B. West,et al.  Respiratory Physiology - the Essentials , 1979 .

[33]  C T DOLLERY,et al.  DISTRIBUTION OF BLOOD FLOW IN ISOLATED LUNG; RELATION TO VASCULAR AND ALVEOLAR PRESSURES. , 1964, Journal of applied physiology.